低剂量阿德福韦酯致低血磷性骨软化症的临床特点及治疗分析

Low-dose Adefovir Dipivoxil-induced Hypophosphatemic Osteomalacia: Four Cases Study

目的探讨低剂量阿德福韦酯(10 mg/d)所致低血磷性骨软化症的临床特点及其治疗方法,以提高临床医生对该病的认识。方法回顾性分析2011年4月—2012年7月本院确诊的4例低剂量阿德福韦酯致低血磷性骨软化症患者的临床资料,总结其临床特点及治疗方法。结果 (1)4例患者中,3例为男性,发病年龄为38～68岁,病程为2～24个月。发病时阿德福韦酯持续用药时间为8～94个月。(2)首发症状以足跟负重痛最为常见(3/4)。主要表现为进行性骨痛(4/4),最常累及足跟和胫前(3/4);踝关节痛(4/4);身高变矮(2/4)。查体发现2例有胸廓、骨盆挤压痛。病史:1例合并高血压,1例长期大量饮酒。(3)实验室检查可见低磷血症(4/4)、高尿磷(4/4)、血碱性磷酸酶(ALP)增高(3/4)。影像学检查:双能骨密度及X线检查显示骨质疏松(4/4);骨扫描可见颅骨、四肢长骨骨皮质普遍放射性增高(3/4)。(4)治疗:停用阿德福韦酯,改为恩替卡韦抗病毒;口服中性磷溶液、阿法迪三胶囊、钙尔奇D片。4～16周时患者的血磷恢复正常,8～20周骨关节痛缓解。随访至11～73周,除1例合并右股骨不全骨折外,其余患者均恢复正常行走能力。结论低剂量阿德福韦酯可导致低血磷性骨软化症。对长期服用阿德福韦酯者老年人、饮酒、合并慢性病者,用药期间应定期监测,尤其是血磷、ALP水平及肾功能、尿常规,以尽早发现,及时给予中性磷治疗。

Objective To investigate the clinical characteristics and treatment approaches of low-dose（10 mg/d） adefovir dipivoxil-induced hypophosphatemic osteomalacia.Methods The clinical data of four cases with low-dose adefovir dipivoxil-induced hypophosphatemic osteomalacia diagnosed in our hospital between April 2011 and July 2012 were analyzed.The clinical features and treatment approaches were summarized.Results Among the four cases： three males,disease onset age 38～68 years,disease course 2～24 months,length of adefovir dipivoxil administration before onset 8～94 months.Heel pain was the most common first symptom（3 /4）.The major clinical presentations included progressive bone pain（4 /4） usually involving heel and tibia（3 /4）,ankle joint pain（4 /4）,and decreased body height（2 /4）.Physical examination found two cases with squeezing pain on thorax and pelvis.One case had a history of hypertension,another long-term heavy drinking.Laboratory tests revealed hypophosphatemia（4 /4）,hyperphosphaturia（4 /4）,and elevated serum alkaline phosphatase level（3/4）.Dual energy X-ray absorptiometry and X-ray showed osteoporosis（4/4）;Bone scan showed pervasive increased radioactivity at skull and limbs long bone（3 /4）.Adefovir dipivoxil was substituted with entecavir,combined with oral neutral phosphate solution,alfacalcidol,and calcium.Serum phosphorus came to normal after 4～16 weeks,bone and joint pain was alleviated after 8～20 weeks.The subjects were followed up for 11～73 weeks,and all restored walking ability except for one patient with incomplete right femur fracture.Conclusion Low-dose adefovir dipivoxil can induce hypophosphatemic osteomalacia.Patient taking long-term adefovir dipivoxil,especially the elderly or those with drinking habit or chronic diseases,should be monitored regularly for serum phosphorus,serum alkaline phosphatase,renal function,and urine routine.Once the adverse effects are found,adefovir dipivoxil should be withdrawn as soon as possible and oral neutral phosphate solution should be administered.